This project is based on the assumption of heterogeneity of schizophrenia. Its objective is to classify schizophrenic patients using measures of sleep staging and REMsleep phasic events such as indices of eye movement activity and middle ear muscle activity and to relate these measurements to neuroleptic responsiveness and CSF neurotransmitter biochemistry. Our current findings suggest that schizophrenia and schizo-affective disorder can be distinguished from major depressive disorder using measures of sleep latency and the amount of waking after sleep onset and that schizo-affective disorder can be distinguished from schizophrenia using measures of REM latency and eye movement activity. Within schizophrenia, a patient clusters can be defined by the rate of REM sleep middle ear muscle activity (MEMA). Pilot data suggest that patients with high MEMA rates may not respond to neuroleptic medication. To reach our objective, we will study 24 patients per year conducting up to 216 allnight sleep recording sessions per year. These patients will meet RDC for schizophrenia (N=12), schizo-affective disorder (N=6), and, as a control for depression, major depressive disorder (N=6). Over a three year period, our anticipated subject pool will include 18 with major depressive disorder, 18 with schizo-affective disorder and 36 schizophrenics. Of this latter, we anticipate that nearly 1/2 will have abnormally elevated rates of middle ear muscle activity. Our aims are: 1) to define sleep stage and REM phasic event markers of schizophrenia and schizo-affective disorder using Ss with major depressive disorder as controls; 2) to relate these markers to CSF neurotransmitter metabolite levels; 3) to relate MEMA rate to clinical status and neuroleptic responsiveness; and 4) to develop a simpler technique for the recording of MEMA.